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The essential oil from Curcumae wenyujin (CWEO) has antibacterial activity, but the antibacterial compounds in the CWEO have not been identified. The spectrum-effect relationship between chemical compositions and pharmacological activity is regarded as a potentially useful tool to screen bioactive compounds. The binary chromatographic fingerprint of CWEO was established by gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/diode-array (HPLC-DAD). A data-level information integration method was used to investigate the chemical characteristics encoded in two chromatographic fingerprints. Additionally, the antibacterial activity against Escherichia coli (E. coli）was determined by the liquid dilution method. The spectrum-effect relationship between the binary chromatographic fingerprint and antibacterial activity was investigated with principal component analysis (PCA) and orthogonal projection to latent structures (OPLS) analysis. Compared with a single data matrix, the combined data matrix allowed more accurate identification of the strong outliers in the PCA. Additionally, the results of OPLS were used to establish a spectrum-effect relationship with a closer correlation than that generated with the single data matrix. The results indicated that germacrone, curdione, and furanodiene were detected in HPLC and GC-MS fingerprints, and may be the main antibacterial components. Abbreviations: CWEO, essential oil from C. wenyujin; MIC, minimum inhibitory concentration; OPLS, orthogonal projection to latent structures. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor-α (TNF- α)is a major contributor to the pathogenesis of insulin resistance associated with obesity and type 2 diabetes. It has been found that endogenous hydrogen sulfide (H2S) contributes to the pathogenesis of diabetes. We have hypothesized that TNF-α-induced insulin resistance is involved in endogenous H2S generation. The aim of the present study is to investigate the role of endogenous H2S in TNF-α-induced insulin resistance by studying 3T3-L1 adipocytes. We found that treatment of 3T3-L1 adipocytes with TNF-α leads to deficiency in insulin-stimulated glucose consumption and uptake and increase in endogenous H2S generation. We show that cystathionine γ-lyase (CSE) is catalysed in 3T3-L1 adipocytes to generate H2S and that CSE expression and activity are upregulated by TNF-α treatment. Inhibited CSE by its potent inhibitors significantly attenuates TNF-α-induced insulin resistance in 3T3-L1 adipocytes, whereas H2S treatment of 3T3-L1 adipocytes impairs insulin-stimulated glucose consumption and uptake. These data indicate that endogenous CSE/H2S system contributes to TNF-α-caused insulin resistance in 3T3-L1 adipocytes. Our findings suggest that modulation of CSE/H2S system is a potential therapeutic avenue for insulin resistance. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Bismuth titanate Bi4Ti3O12 was prepared by using the chemical solution decomposition (CSD) method. The obtained powders were characterized by X-ray diffraction (XRD), UV-Vis spectroscopy. Photocatalytic property of Bi4Ti3O12 crystals was evaluated by using methyl orange as a model organic compound. The factors affecting the photocatalytic activity, such as calcination condition for the photocatalyst, the pH value of the reaction suspension, the strong oxidant species additives H2O2 and the addition of NaCl, NaNO3 and K2SO4 into the suspension, have been studied. The band gap energy value for Bi4Ti3O12 compound is 3.08 eV observed by a UV-Vis recording spectrophotometer. Bi4Ti3O12 exhibits photocatalytic activities to photodegrade methyl orange. The bond angle of Ti&z.sbnd;O&z.sbnd;Ti in Bi4Ti3O12 and the formed intra-electric field between the (Bi2O2)2+ layer and the (Bi2Ti3O10)2- layer are assumed to motivate the separation of the photogenerated electrons–holes pairs and then improve the photocatalytic activity of the catalysts. [Copyright &y& Elsevier]

Purpose: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. Methods: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). Result: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80–1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88–1.70, P = 0.238). Conclusion: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection. [ABSTRACT FROM AUTHOR]

Background Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (LncRNA MALAT1) has been proven to promote osteogenesis in different health conditions. However, the role of plasma MALAT1 in postmenopausal osteoporosis (PMOP) has not been investigated. Objective To investigate whether plasma MALAT1 expressions are associated with severity of PMOP. Methods A total of 126 patients with PMOP and 126 healthy female control individuals were drafted into study participation. Plasma MALAT1 was detected using RT-PCR. Bone formation marker bone-specific alkaline phosphatase plasma concentration was determined using chemiluminescence immunoassay. Levels of bone absorption marker cross-linked N-telopeptidases of type I collagen were measured in duplicate using enzyme immunoassay. Bone mineral density (BMD) was examined in the total hips, femoral neck, and lumbar (L1–L4) spine using dual-energy x-ray absorptiometry. We used Genant semiquantitative (GSQ) criteria to assess the degree of vertebral deformity and fracture. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the potential diagnostic value of MALAT1 with regard to the GSQ grading. We used the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) to evaluate the symptomatic severity in and functional ability of the study participants. Results Plasma MALAT1 expressions were significantly lower in patients with PMOP, compared with healthy controls. Plasma MALAT1 expressions in patients with PMOP were positively associated with total hip, femoral neck, and lumbar (L1–L4) spine BMD. In total, 95 patients experienced vertebral deformity or fracture (VF), and 31 had no fractures. Plasma MALAT1 expressions were markedly decreased in patients with VF, compared with patients without fractures. Plasma MALAT1 expressions were negatively related to GSQ grading in patients with VF. ROC curve analysis demonstrated that decreased plasma MALAT1 expression exhibits decent diagnostic value with regard to GSQ grading. Finally, we discovered that plasma MALAT1 expression was also negatively associated with VAS and ODI. Conclusion Plasma MALAT1 expressions are negatively associated with severity of PMOP. [ABSTRACT FROM AUTHOR]

Leech, as a traditional Chinese medicine for the treatment of blood circulation and blood stasis, was also widely used to cure pulmonary fibrosis in China. In clinical practice, some traditional Chinese medicine preparation such as Shui Zhi Xuan Bi Hua Xian Tang and Shui Zhi Tong Luo Capsule composed of leech, could improve the clinical symptoms and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the material basis of the leech in the treatment of IPF were not yet clear. Screen out the components of leech that have the anti-pulmonary fibrosis effects, and further explore the therapeutic mechanism of the active components. In this study, the different molecular weight components of leech extract samples were prepared using the semi-permeable membranes with different pore sizes. The therapeutic effects of the leech extract groups with molecular weight greater than 10 KDa (>10 KDa group), between 3 KDa and 10 KDa (3–10 KDa group), and less than 3 KDa (<3 KDa group) on pulmonary fibrosis were firstly investigated by cell proliferation and cytotoxicity assay (MTT), cell wound healing assay, immunofluorescence staining (IF) and Western blot (WB) assay through the TGF-β1-induced fibroblast cell model. Then bleomycin-induced pulmonary fibrosis (BML-induced PF) mouse model was constructed to investigate the pharmacological activities of the active component group of leech extract in vivo. Pathological changes of the mouse lung were observed by hematoxylin-eosin staining (H&E) and Masson's trichrome staining (Masson). The hydroxyproline (HYP) content of lung tissues was quantified by HYP detection kit. The levels of extracellular matrix-related fibronectin (FN) and collagen type Ⅰ (Collagen Ⅰ), pyruvate kinase M2 (PKM2) monomer and Smad7 protein were determined via WB method. PKM2 and Smad7 protein were further characterized by IF assays. Using TGF-β1-induced HFL1 cell line as a PF cell model, the in vitro results demonstrated that the >10 KDa group could significantly inhibited the cell proliferation and migration, downregulated the expression level of cytoskeletal protein vimentin and α-smooth muscle actin (α-SMA), and reduced the deposition of FN and Collagen Ⅰ. In the BML-induced PF mouse model, the >10 KDa group significantly reduced the content of HYP, downregulated the expression levels of FN and Collagen Ⅰ in lung tissues, and delayed the pathological changes of lung tissue structure. The results of WB and IF assays further indicated that the >10 KDa group could up-regulate the expression level of PKM2 monomer and Smad7 protein in the cellular level, thereby delaying the progression of pulmonary fibrosis. Our study revealed that the >10 KDa group was the main material basis of the leech extract that inhibited pulmonary fibrosis through TGF-β1/Smad3 signaling pathway. [Display omitted] • Classify the leech extract group with molecular weight. • The >10 KDa group best inhibited the activity of TGF-β1-induced fibroblast. • The >10 KDa group significantly alleviated BLM-induced pulmonary fibrosis in mice. • The >10 KDa group attenuated IPF in TGF-β1/Smad3 signaling pathway. [ABSTRACT FROM AUTHOR]

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified to facilitate osteogenic differentiation and bone formation both in vitro and in vivo. However, whether lack of PACAP is associated with osteoporosis (OP) still remains unknown. The scope of the current study was to examine the potential relationship between serum PACAP concentrations and disease severity in female patients with postmenopausal osteoporosis (PMOP). 123 PMOP females were enrolled in our study. During the same period, BMI and age-matched 120 postmenopausal non-osteoporotic (PMNOP) patients were also recruited as control. Serum PACAP concentrations were determined by Sandwich ELISA. Bone mineral density was examined by dual-energy x-ray absorptiometry (DXA) at the total hip, lumbar 1–4 vertebrae and left femoral neck. Genant grade was utilized for evaluating the degree of vertebral fracture and receiver operating characteristic (ROC) curve was performed to examine the diagnostic value of PACAP with regard to Genant grade. The numerical rating scale (NRS) was applied for test pain and 6-min walking as well as sit-to-stand test was used for functional status. The bone turnover markers including N-terminal propeptide of type I procollagen (PINP) (marker of bone formation) and C-telopeptide of type I collagen (CTX-I) (marker of bone resorption) were also examined. The PMOP women had significantly decreased mean serum PACAP levels in comparison with the PMNOP females. Serum levels of PACAP in vertebrae fracture patients were significantly lower than that in non-fracture patients Serum PACAP concentrations were negatively and significantly related to Genant grade as well as BMD at total hip, lumbar 1–4 vertebrae and left femoral neck. Further ROC analysis indicated that PACAP may act as a decent marker for Genant grade. In addition, serum PACAP levels were negatively associated with NRS and positively related to 6-min walking as well as sit-to-stand test scores. Last, we found PACAP were negatively correlated with increased CTX-I levels and positively related to PINP levels. Attenuated PACAP concentrations were related to disease severity of PMOP, PACAP may act as a protective role during PMOP. [ABSTRACT FROM AUTHOR]

Background: Postprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of short-term postprandial glucose (PPG) excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD. However, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with acute coronary syndrome (ACS). Methods: A total of 144 diabetic patients with ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 49 patients with plaque rupture and 95 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBG), hemoglobin A1c (HbA1c) and 1,5-AG levels were measured before coronary angiography. Fasting urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) level was measured and corrected by creatinine clearance. Results: Patients with ruptured plaque had significantly lower serum 1,5-AG levels, longer duration of diabetes, higher HbA1c and FBG levels than patients without ruptured plaque in our study population. In multivariate analysis, low 1,5-AG levels were an independent predictor of plaque rupture (odds ratio 3.421; P = 0.005) in diabetic patients with ACS. The area under the receiver-operating characteristic curve for 1,5-AG (0.658, P = 0.002) to predict plaque rupture was superior to that for HbA1c (0.587, P = 0.087). Levels of 1,5-AG were significantly correlated with urinary 8-iso-prostaglandin F2α levels (r = − 0.234, P = 0.005). Conclusions: Serum 1,5-AG may identify high risk for coronary plaque rupture in diabetic patients with ACS, which suggests PPG excursions are related to the pathogenesis of plaque rupture in diabetes. [ABSTRACT FROM AUTHOR]

Background: The neuropeptide vasoactive intestinal peptide (VIP) has been identified as inhibiting osteoclastogenesis and suppressing inflammation. Objective: This study was conducted to examine serum VIP levels in postmenopausal osteoporosis (PMOP) patients and explore the correlation of serum VIP levels with disease severity of PMOP. Methods: A total of 106 postmenopausal women diagnosed as osteoporotic were enrolled in the study and 102 postmenopausal women with normal bone mineral density (BMD) were enrolled as controls. BMD at the femoral neck (FN), lumbar spine 1–4, and total hip were examined using dual-energy X-ray absorptiometry. Genant semiquantitative grading was used for vertebral morphometry and fracture. Serum VIP levels were tested using enzyme-linked immunosorbent assay. Serum inflammatory factor interleukin-1β (IL-1β), osteoclastic activity marker tartrate-resistant acid phosphatase 5b (TRACP-5b), and estrogen-2 (E2) were also examined. Receiver operating characteristic (ROC) analyses was performed to determine the diagnostic values of serum VIP, IL-1β, TRCAP-5, and E2 with regard to Genant grade. Results: Our findings demonstrated a reduction in the serum level of VIP expressed in PMOP patients compared with controls. In the PMOP group, patients with lumbar fracture had significantly lower serum VIP concentrations in comparison with healthy controls. Serum VIP concentrations were positively associated with BMD at the FN, lumbar spine 1–4, and total hip. We also observed that serum VIP levels were positively correlated with E2 levels but negatively correlated with IL-1β and TRCAP-5 levels. In addition, ROC analysis found that reduction of serum VIP in combination with elevation of TRACP-5b may serve as an indicator of a severe Genant grade. Conclusions: Attenuated serum VIP levels were linked to disease severity of PMOP and may act as a protective marker for PMOP. [ABSTRACT FROM AUTHOR]

Highlights • Although the toxicity of KPC on normal rats was stronger than KA, KPC exhibited better efficacy to malignant ascites with little side effects. • Novel UPLC-MS/MS methods for determination of kansuiphorin C and kansuinin A in rat feces were established. • The quicker accumulative excretion rate of KPC in rat feces than KA within 48 h indicating the potential different interactions with microbiota. Abstract Malignant ascites (MA) is one of the severe complications of gastrointestinal tumors, affecting the patients' survival time and quality of life. Euphorbia kansui is a commonly used toxic Chinese herbal medicine for malignant ascites. Our previous study showed that the biological and toxicological effects of kansui were closely related to the gastrointestinal tract. The ingenane-type and jastrophane-type diterpenoids are both toxic and active components of kansui. The contents of kansuiphorin C (KPC) and kansuinin A (KA) take highest accounts in each type of diterpene. Hence, in this study, the efficacy and toxicity of KPC and KA on normal rats and MA rats were firstly evaluated by serum liver enzymes (ALT and AST), oxidative damage indicators (GSH, SOD, MDA and LDH), inflammatory indexes (TNF-α, IFN-γ and IL-2) and the volume of ascites. Changes in the levels of these indices showed that although the toxicity of KPC on normal rats was stronger than KA, KPC exhibited better efficacy to the malignant ascites with no obvious side effects at the dose of 10 mg·kg−1. Then, accurate and reliable methods for the determination of KPC and KA in the rat feces by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) were established, detected by the multiple reaction monitoring mode. The chromatographic separation was conducted on an XBbridge C18 column (50 mm × 2.1 mm, 2.5 μm) using gradient elution composed of 0.1% formic acid in water and acetonitrile. The flow rate was 0.5 mL·min−1 and column temperature was 30 °C. The method was finally applied to the comparative study on normal and malignant ascites rats given KPC and KA, respectively. Interestingly, the results showed that KPC's accumulative fecal excretion rate (normal, 19.22%±5.36%; model, 15.96%±3.47%) were much higher than that of KA (normal, 2.928%±0.741%; model, 2.835%±0.873%) at the same dose within 48 h. This suggested KPC had higher in-vivo transformations in comparison with KA, providing guidance for the further preclinical research of KPC and KA as promising compounds treating MA. [ABSTRACT FROM AUTHOR]

The traditional processing method for the slices preparation of Rehmanniae roots is time- and energy-consuming and is prone to result in loss of active components during twice water-treatment (once for wash and the other for softening) and drying steps. In this study, we firstly explored an integrative processing technique for Rehmanniae Radix by 2x3 factorial experiment based on the contents of catalpol and verbascoside as measured by HPLC. The potential differences between the traditional stepwise processing technique and the integrative processing technique for catalpol and verbascoside in the prepared slices were investigated. To further confirm the effectiveness of drugs using the integrative processing technique, some pharmacological variables, such as rectal temperature, hematologic parameters (RBC, HGB, HCT, and blood viscosity), and coagulation parameters (TT, APTT, PT and FIB), were detected in a blood-heat and hemorrhage syndrome rat model. Two-way ANOVA analysis showed that drying for 18 h at 50°C was considered as the best combination of process conditions. The mean catalpol and verbascoside contents in the integrative method-processed samples (4.30% and 0.33%, respectively) were higher than those in the traditional method-processed samples (2.61% and 0.21%, respectively). Significant increases in rectal temperature, and hematologic parameters, TT, APTT, and FIB, were observed in the model group rats, compared to the blank group animals (P<0.01). Both in the integrative groups and traditional groups, the extracts caused significant decreases in rectal temperature, RBC, HGB, and HCT with increased concentration compared to the model group animals. All coagulation parameters tested were shortened in model rats received two kind prepared slices. There were no significant therapeutic differences between the integrative and the traditional method-processed slices on the hemostasis and hemorheological parameters in this blood-heat and hemorrhage syndrome rat model, indicating that our integrative method may be a feasible technique for processing Rehmanniae Radix slices. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Kansui, the root of Euphorbia kansui S.L.Liou ex S.B.Ho ( E.kansui ), is a classical traditional Chinese medicine (TCM) with certain toxicity. According to the theory of TCM, kansui fry-baked wtith vinegar (VEK) possesses low toxicity and mild diuretic and purgative efficacy. In clinical practice, it is commonly used for the treatmtablent of ascites and oliguria. The present study aimed to evaluate the toxicity and efficacy of different fractions of VEK and reveal the underlying material basis by employing an animal model of malignant ascites effusion (MAE) in rats. Materials and methodsta The MAE rats as the model were constructed in SPF male wistar rats by intraperitoneal injection of Walker-256 tumor cells. The MAE rats were used and randomly divided into the control group (normal rats), control groups with different fractions (VEKA, VEKB, VEKC and VEKD), model group (MAE rats), positive control group (model group with furosemide), model groups with different fractions (VEKA, VEKB, VEKC and VEKD). Histopathological observation was used to confirm Walker-256 tumor-bearing organ injuries in rats. For the efficacy evaluation, the ascites and urine volumes, the urinary electrolyte concentrations (Na + , K + and Cl - ) and pH, the ascites levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, IFN-γ and VEGF), PRA, the serum levels of Ang II, ALD and ADH, as well as AQP8 protein expression in the gastrointestinal tract were detected. Furthermore, different levels of indicators were measured in the toxicity evaluation of different fractions both on normal and model rats, including serum liver enzymes (AST and ALT), serum oxidative damage parameters (GSH, MDA, LDH and SOD), expressions of inflammatory parameters (NF-κB, ICAM-1 and E-cadherin) and apoptosis signals (caspase-3, −8, −9, Bcl-2 and Bax) in the liver and gastrointestinal tract. Results Walker-256 tumor-bearing malignant ascites effusion rats showed obvious hepatic and gastrointestinal injuries by histopathological observation. In the efficacy evaluation, model rats treated with VEKB and VEKC showed significant urine increase (VEKB, P  < 0.01; VEKC, P  < 0.01) and ascites reduction (VEKB, P  < 0.01; VEKC, P  < 0.01). These two fractions also balanced the concentrations of Na + , K + and Cl - in urine (VEKB, all P  < 0.05; VEKC, all P < 0.05), remarkably decreased urinary pH (VEKB, P  < 0.01; VEKC, P  < 0.01), and reduced the ascites levels of IL-2, IL-6, TNF-α, IFN-γ and VEGF (VEKB, all P  < 0.01; VEKC, all P  < 0.01) in the model rats. Moreover, levels of PRA, the serum Ang II, ALD and ADH of model rats were decreased after treated by VEKB and VEKC (VEKB, all P  < 0.05; VEKC, all P  < 0.05). Meanwhile, the expression of gastrointestinal AQP8 of the model rats was also enhanced after treated by VEKB and VEKC (VEKB, P  < 0.01; VEKC, P  < 0.01). In the toxicity evaluation, although VEKB and VEKC caused toxic indexes moved to the worse aspects in normal rats, nearly all of these indicators notably improved in the model rats. Additionally, VEKA showed no effect on the indicators, either in the efficacy evaluation or in the toxicity evaluation. And VEKD could significantly improve some indicators (urine volume, concentration of K + in urine, serum MDA, AI and caspase-9) in MAE rats. Conclusions VEKB and VEKC were demonstrated a significant efficacy in treating malignant ascites effusion, which could reduce hepatic and gastrointestinal damage on the model rats but cause the same damage to the normal. These data embody the traditional Chinese medicine application principle: You Gu Wu Yun . And these results will provide reference for the safer and better clinical utilization of kansui. [ABSTRACT FROM AUTHOR]

The dried roots of Euphorbia kansui T.N. Liou ex T.P. Wang have been traditionally used for edema in China. However, the severe toxicity caused by Euphorbia kansui has seriously restricted its clinical application. Therefore, in order to study the material basis of the toxicity attenuation effect of processing with vinegar, a rapid, sensitive, validated and reliable UPLC–MS/MS method was developed to determine twelve compounds in ethyl acetate extracts of Euphorbia kansui before and after fry-baked with vinegar simultaneously. Meanwhile, the study of their toxic effect on zebrafish was conducted. Chromatographic separation was accomplished on Waters BEH C 18 UPLC column. 0.3% formic acid in water and acetonitrile were used as mobile phase with a flow rate of 0.40 mL/min and a temperature at 30 °C. The analysis was performed in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). Furthermore, the toxic research results indicated that the toxicity of Euphorbia kansui was decreased after vinegar-processed, which might because of the increase in the content of 5- O -benzoyl-20-deoxyingenol and the decrease in the contents of the remaining terpenoids in ethyl acetate extracts of Euphorbia kansui fry-baked with vinegar. This study demonstrated that the method used is a powerful approach to determine the content of twelve compounds that responsible for the toxic effect of Euphorbia kansui at the same instant. And provided the experimental evidence for the rationale behind the reduction of toxicity. [ABSTRACT FROM AUTHOR]

Background: The correlation between the atherogenic index of plasma (AIP) and waist circumference (WC) remains unknown. Methods: A total of 5351 middle-aged men living in Southeastern China were surveyed using the random stratified cluster sampling method. A WC of 90 cm or greater was indicative of abdominal obesity, and AIP was calculated as follows: log [triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C)]. Results: (1) A significantly higher AIP was observed in subjects with abdominal obesity than in those without abdominal obesity (P < 0·001). (2) Multivariate logistic regression analysis revealed an odds ratio of 1·93, 2·59 and 2·76 for abnormal AIP levels for the second, third and fourth WC quartiles, respectively (all P < 0·001) compared to the first WC quartile as a reference. (3) There was a linear correlation between WC and AIP, and a 1·0 cm increase in WC resulted in a 0·0175 rise in AIP. For AIP corresponding to moderate risk (0·12-0·21), WC was 85-90 cm; for AIP corresponding to high risk (> 0·21), WC was >90 cm. Conclusions: AIP of 0·12-0·21 or >0·21 indicates a likelihood of borderline abdominal obesity or abdominal obesity, respectively, and the combination of WC and AIP may increase the specificity and sensitivity for detection of abdominal obesity in clinical practice. The results suggest that AIP may be used as a reference to estimate abdominal obesity. [ABSTRACT FROM AUTHOR]

• A microRNA upconversion cycling nanoamplicon sensing platform was fabricated. • 8–17 DNAzymes were employed as nanoamplicon. • The nanoprobe showed high LRET efficiency of 60.9% for BHQ1 as the energy acceptor. • The nanoprobe achieved a linear range from 4 × 10-14 M to 1 × 10-8 M with LOD of 31 fM. • The nanoprobe was successfully applied to in - vitro and in - vivo imaging of miR-21. Upconversion nanoparticles (UCNPs) are promising materials for imaging biomolecules and predicting the progression of diseases, especially for tumors. However, conventional luminescence resonance energy transfer (LRET) based nanosensors remain challenging with complicated modification and unsatisfactory sensitivity. Herein, a sensing platform integrating confined emission effect and cycling amplification strategy into one substrate with high LRET efficiency and sensitivity has been developed for the in - vitro and in - vivo detection of microRNA-21. Washing UCNPs with hydrochloric acid was conducted for electrostatic absorption of 8–17 DNAzyme labeled with BHQ1 (8–17 DNAzyme-BHQ1) and complementary capturing template-aDNA3 complex (CPT-aDNA3) to form energy donor–acceptor pair (UCNPs-BHQ1) and capture miR-21. It not only avoids the complex modification procedure but also shortens the distance between the donor (UCNPs) and the acceptor (BHQ1). The quenching efficiency of 60.94 % was obtained. Targeted miR-21 could bind with CPT to release aDNA3 that can unlock 8–17 DNAzyme-BHQ1 to form aDNA3-DNAzyme-BHQ1 duplex. This aDNA3-DNAzyme-BHQ1 duplex owning -rA- group can be cleaved by Zn2+ so that UCNPs restored green UCL emission because of the desorption of BHQ1. aDNA3 becomes dissociative again to trigger the next cycle. This UCNP@DNAzyme-BHQ1/CPT- aDNA3 achieved a wide linear range from 4 × 10-14 M to 1 × 10-8 M with a low limit detection of 31 fM for the sensitive detection of miR-21 in vitro. Furthermore, it was successfully applied to the real-time intracellular detection of miR-21 in HeLa cells and in - vivo monitoring of miR-21 expression in KS-01 treated tumor-bearing mouse. This proposed DNA-conjugated upconversion nanoamplicon provides new sights into monitoring of anti-cancer active ingredients efficacy and the progress evaluation of miRNA-related diseases. [ABSTRACT FROM AUTHOR]

Chinese herbal medicines (CHMs) have been widely used to treat disease in China. However, their unstable quality, vague active compounds and ambiguous effects in vivo make most people suspicious of them. Therefore, it is promising to develop strategies for assuring the quality, discovering active compounds, monitoring the in-vivo biological process, and improving the efficacy of CHMs. Combining novel nanomaterials with multiple analytical and imaging modalities becomes a rising solution to these problems. In this review, analytical and biomedical applications of nanomaterials in CHMs field with an emphasize on their merits are highlighted, including hazardous substances detection, screening and quantification of active compounds, the toxicity and pharmacological evaluation, the optimization of therapeutic efficacy and the component enrichment. There is no doubt that the application of nanomaterials in CHMs provides researchers new guidelines and it has long-term prospects if some shortcomings are overcome. [Display omitted] • Analytical and biomedical applications of common nanomaterials in Chinese herbal medicines research are well detailed. • Key challenges and prospects for nanomaterials-based Chinese herbal medicines research are discussed. [ABSTRACT FROM AUTHOR]

Background Intestinal ischemia–reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR. Methods Thirty-two Sprague–Dawley rats were randomly divided into four groups ( n = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot. Results Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity ( P < 0.05). PNU treatment could significantly improve the pulmonary function of rats subjected to IIR. These effects of activation of α7nAChR were associated with suppression of TLR4/NF-κB pathway and subsequent reduction of apoptosis-related protein. However, MLA treatment aggravated lung injury. Conclusions α7nAChR plays a role in acute lung injury induced by IIR via attenuating lung oxidative stress and inflammation through suppression of TLR4/NF-κB pathway, resulting in reduction of apoptosis in the lung. [ABSTRACT FROM AUTHOR]

The major purpose of this study was to assess the association between the potential long-term effects of previous schistosome infection and atherogenic dyslipidemia. Among 1597 men aged ⩾45 years who received health examinations and lived in previous schistosomiasis-endemic regions of China, 465 patients with previous schistosome infection were selected as study subjects, and 1132 subjects formed the control group. The risk factors for cardiovascular disease were measured and compared between the previous schistosome infection and control groups. The Atherogenic Index of Plasma, triglycerides, waist circumference and body mass index were significantly lower in the previous schistosome infection group than in the control group (all P values <0.001), whereas high-density lipoprotein–cholesterol was significantly higher in the previous schistosome infection group ( P < 0.001). In the Atherogenic Index of Plasma quartiles (Q1–Q4), the percentages of subjects with previous schistosome infection were 55.89% (Q1), 25.44% (Q2), 16.33% (Q3), and 18.8% (Q4), respectively ( χ 2 = 139.86, P < 0.001). A logistic regression analysis based on previous schistosome infection as the independent variable and Atherogenic Index of Plasma as the dependent variable revealed that previous schistosome infection was significantly negatively correlated with Atherogenic Index of Plasma (odds ratio = 0.583, 95% confidence interval: 0.440–0.772, P < 0.001) after adjustment for body mass index, waist circumference, diastolic blood pressure and uric acid, suggesting that previous schistosome infection is an independent factor associated with Atherogenic Index of Plasma. The potential long-term effects of previous schistosome infection may reduce the Atherogenic Index of Plasma in Chinese men. However, further studies are required to investigate the protective human immune response against schistosome infections. The development of a schistosomiasis vaccine may effectively prevent the development and progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Short-term voltage stability is an increasing concern in today's power systems due to the growing penetration of induction motors. This paper proposes a systematic method for optimal placement of dynamic VAR support against short-term voltage instability. The problem is formulated as a multi-objective optimization model minimizing two conflicting objectives: 1) the total investment cost and 2) the expected unacceptable short-term voltage performance subject to a set of probable contingencies. STATCOM is employed for its stronger dynamic VAR support capability. Indices for quantifying the short-term voltage stability and the related risk level are proposed for problem modeling. Candidate buses are selected based on the concept of trajectory sensitivity. Load dynamics are fully considered using a composite load model containing induction motor and other typical components. A relatively new and superior multi-objective evolutionary algorithm called MOEA/D is introduced and employed to find the Pareto optimal solutions of the model. The proposed method is verified on the New England 39-bus system using industry-grade models and simulation tool. [ABSTRACT FROM AUTHOR]

Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it's toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it's toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research. [Display omitted] • A simultaneous determination of four compounds in EP and VEP using UPLC was established. • Toxicity of them was evaluated on zebrafish embryos, and they possessed cardiotoxicity, liver and gastrointestinal toxicity. • The toxicity mechanism was related to oxidative damage and the up-regulation of expression of apoptosis-associated genes. [ABSTRACT FROM AUTHOR]

Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG，fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. Aim of the study : We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl−) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT. Image 1 [ABSTRACT FROM AUTHOR]

Malignant ascites (MA) effusion is mainly caused by hepatocellular, ovarian, and breast cancer etc. It has been reported that Euphorbia kansui (EK), the root of Euphorbia kansui S.L.Liou ex S.B.Ho, possessing a therapeutic effect on MA. However, the clinical applications of EK are seriously restricted for its severe toxicity. Although studies demonstrated that vinegar-processing can reduce the toxicity and retain the water expelling effect of EK, its specific mechanism remains unknown. This study aims to explore the underlying mechanisms of toxicity reduction without compromising the pharmacological effects of EK stir-fried with vinegar (VEK). 3- O -(2′ E ,4′ Z -decadienoyl)-20- O -acetylingenol (3- O -EZ), a major diterpenoid of EK, could convert into ingenol after processing EK with vinegar. The H22 mouse hepatoma ascites model was replicated, and were given 3- O -EZ and ingenol seven days (110.14, 50.07 and 27.54 mg/kg). The histopathological observation, serum liver enzymes, serum Renin-Angiotensin-Aldosterone System (RAAS) levels, ascites volumes, pro-inflammatory cytokines levels and H22 cells apoptosis in ascites were examined. Then the intestine (Aquaporin 8, AQP8) and kidney (Aquaporin 2, AQP2; Vasopressin type 2 receptor, V2R) protein expression were detected, as well as the metabolomics of serum were analyzed. Finally, the content of 3- O -EZ and ingenol in EK and VEK were investigated. 3- O -EZ and ingenol can relieve hepatic and gastrointestinal injuries, reduce ascites volumes, enhance the H22 cells apoptosis, ameliorate abnormal pro-inflammatory cytokines and RAAS levels, and down-regulate the expression of AQP8, AQP2, V2R. The involved metabolic pathways mainly included glycerophospholipid metabolism and arachidonic acid metabolism. And the decreasing rate of 3- O -EZ in VEK was 19.14%, the increasing rate of ingenol in VEK was 92.31%. 3- O -EZ and ingenol possess significant effect in treating MA effusion, while ingenol has lower toxicity compared with 3- O -EZ. And provide evidence for the mechanism of attenuation in toxicity without compromising the pharmacological effects of VEK. Image 1 [ABSTRACT FROM AUTHOR]

• A simultaneous determination of six ingenane-type diterpenoids in EK and VEK using UFLC-MS/MS was established. • After stir-fried with vinegar, toxic ingenane-type diterpenoids converted to less toxic compounds with retained activity. • Toxicity of six ingenane-type diterpenoids was evaluated on zebrafish embryos. • Ingenane-type diterpenoids could increase the expression of AQP3 protein to expel water in the colon. The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1) , 5- O -benzoyl-20-deoxyingenol (2) , 20-deoxyingenol (3) , 3- O -(2' E ,4' E -decadienoyl)-20- O -acetylingenol (4) , 20- O -(2' E ,4' Z -decadienoyl)ingenol (5) , and ingenol (6) , in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min−1. Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1 , 2 , 4 , and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC 50 > 200 μM). Meanwhile, 1 , 2 , 4 , 5 , and 6 significantly increased the expression of AQP3 protein (p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine (TCM) the root of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), is used for treating edema and ascites but is also of toxicological concerns. And the clinical applications of EK have been seriously restricted for its severe toxicity. To reduce its toxicity, a commonly used clinical practice is processing it with vinegar. This review aimed to summarize and discuss updated information on biological activities and phytochemistry of EK before and after vinegar-processing, and provide feasible insights for further research on the chemical composition, toxicity and pharmacological effects of EK before and after vinegar-processing. The relevant information on chemical compositions and biological activities of EK before and after vinegar-processing was collected from scientific databases (Google Scholar, PubMed, CNKI, SpringerLink, Web of Science, Wiley Online Library and SciFinder). Additionally, published and unpublished Ph.D. and MSc. dissertations were also obtained from online databases. Diuretic and purgative effect of EK are well documented pharmacologically as are acute, irritant and organic toxic effects. Some of about terpenoids reported have antiproliferative effects on cancer cells and potential antiviral effect. After processing with vinegar, the contents of terpenoids mostly were reduced (ingenane and jatrophane type) with some new compounds being generated (unclear). Also, the toxicity of EK was decreased (using mice, rats and zebrafish embryos model), while the diuretic and purgative effects were retained (using cancerous ascites model rats and mice). While some evidence exists for the reduction of toxicity without compromising the pharmacological effects of EK after vinegar processing, the specific mechanism of action remains unknown. Consequently, further research is necessary to investigate the mechanisms and the relationship between vinegar processing and changes in the chemical composition as well as pharmacological effects/toxicity. This is essential before a safe clinical use can be endorsed. Image 1 [ABSTRACT FROM AUTHOR]

Euphorbia kansui is a toxic Chinese herbal medicine and exhibits promising treatment to the malignant ascites (MA) in its traditional use. Ingenane-type and jastrophane-type diterpenes are demonstrated to be responsible for the toxicity and efficacy of kansui. Two representative compounds, kansuiphorin C (KPC) and kansuinin A (KA) in each type were proved to effectively reduce the ascites. The biological and toxicological effects are closely associated with the gastrointestinal tract, but the possible mechanism and related metabolic functions of KPC and KA treating MA through modulating the gut microbiota remain unclear. To investigate the possible mechanism and related metabolism of KPC and KA ameliorating malignant ascites through modulating gut microbiota. MA rats and normal rats were divided into different groups and administrated with KPC, KA, and positive drug, respectively. 16S rDNA gene sequencing and metagenomes analysis combined with the quantification of short-chain fatty acids of feces were performed to reflect the modulation of gut microbiota. Then, the metabolites of KPC and KA in rat feces under the normal and pathological circumstances were detected by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) to explore the in-vivo bacterial biotransformation. KPC and KA were modulatory compounds for gut microbiota. The richness of Lactobacillus and the decreased abundance of Helicobacter involved in the carbohydrate metabolism and amino acid metabolism could be responsible for their prohibitory effects on malignant ascites. KPC exhibited stronger modulation of gut microbiota through making the abundance of Helicobacter about 3.5 times lower than KA. Besides, in-vivo microbial biotransformation of KPC and KA contained oxidation, hydrolysis, dehydration, and methylation to form metabolites of lower polarity. Besides, at the dosage of 10 mg kg−1, the toxicity of both compounds had weaker influences on the gut microbiota of normal rats. KPC and KA could ameliorate malignant ascites by modulating gut microbiota mainly containing the increase of Lactobacillus and the decrease of Helicobacter and related carbohydrate and amino acid metabolism, providing a basis for their promising clinical usage. Image 1 [ABSTRACT FROM AUTHOR]

Eclipta prostrata , a traditional herbal medicine, has long been used in Asia and South America for the therapy of hemorrhagic diseases (e.g. hemoptysis, hematemesis, hematuria, epistaxis and uterine bleeding), skin diseases, respiratory disorders, coronary heart disease, hair loss, vitiligo, snake bite and those caused by the deficiency of liver and kidney. In this review, we highlight relatively comprehensive and up-to-date information of E. prostrata on traditional uses, phytochemistry, pharmacology and toxicity, along with featuring the gaps in current knowledge, aiming to provide references for future research and possible opportunities for well applications of this medicinal plant. Information on E. prostrata was gathered from scientific databases (Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed and CNKI). Information was also obtained from local books, Ph.D. theses and M.Sc. dissertations and Chinese Pharmacopoeia. The plant taxonomy was validated by the database "The Plant List". Various phytochemical classes has been identified and isolated from the plant covering triterpenes, flavonoids, thiopenes, coumestans, steroids and others. Among these, coumestans are reported as the most common ingredients. The isolated crude extracts and individual compounds have been reported to exhibit promising pharmacological properties, such as hepatoprotective, osteoprotective, cytotoxic, hypoglycaemic, anti-inflammatory, anti-microbial, hypolipidemic, promoting hair growth, rejuvenative and neuroprotective effects. Until now, significant progress has been witnessed in phytochemistry and pharmacology of E. prostrata. Thus, some traditional uses has been well supported and clarified by modern pharmacological studies. Moreover, E. prostrata also showed therapeutic potential in some refractory diseases such as cancer, dementia and diabetes. But, present findings are still insufficient that cannot satisfactorily explain some mechanisms of action. More well-designed studies in vitro especially in vivo are required to establish links between the traditional uses and bioactivities, discover new skeletons and activity molecules, as well as ensure safety before clinical use. Image 1 [ABSTRACT FROM AUTHOR]

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics. [ABSTRACT FROM AUTHOR]

Background: Pure laparoscopic radical resection of hilar cholangiocarcinoma is still a challenging procedure, in which laparoscopic lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy were included [1-4]. Relative report is rare in the world up to now. Hilar cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis or vessel invasion [5, 6]. We recently had a patient who underwent a pure laparoscopic extended right hepatectomy and lymph node dissection and hepaticojejunostomy for a type IIIa hilar cholangiocarcinoma.Methods: The tumor was 20 × 15 × 12 mm in diameter and located in the right bile duct and common hepatic duct. Radiological examination showed that hepatic artery and portal vein was not invaded. After the division and mutilation of the right hepatic artery and the right portal vein, short hepatic veins were divided and cut off with clip and ultrasound knife from the anterior face of the vena cava. Mobilization was performed after the devascularization of the right liver, followed by the transection of liver parenchymal with CUSA and ultrasound knife. Finally, left hepatic bile duct jejunum Roux-en-Y reconstruction was performed.Results: This patient underwent successfully with a totally laparoscopic procedure. An extended right hepatectomy (right hemihepatectomy combined with caudate lobectomy) and complete lymph node dissection and hepaticojejunostomy were performed in this operation. The operation time was nearly 590 min, and the intraoperative blood loss was about 300 ml. No obvious complication was observed and the postoperative hospital stay was 11 days. The final diagnosis of the hilar cholangiocarcinoma with no lymph node metastasis was pT2bN0M0 stage II (American Joint Committee on Cancer, AJCC).Conclusions: Pure laparoscopic resection for hilar cholangiocarcinoma was proved safe and feasible, which enabled the patient to recover early and have an opportunity to receive chemotherapy as soon as possible. We present a video of the described procedure. [ABSTRACT FROM AUTHOR]